Establishment of antigen-specific immunotherapy with artificial lymphocytes genetically engineered by antigen specific receptor and functional genes.

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Antigen-specific T lymphocytes should be clonally accumulated in order to perform their roles. We have established a system to detect such accumulated T lymphocytes in a lymphocyte population using RT-PCR and SSCP method on T cell receptor (TCR). We then extended our work to reconstitute the TCR function in vitro. With this method, artificial lymphocytes for antigen-specific immunotherapy could be generated. Two technical difficulties exist. They are the pairing of two TCR messages from a single T lymphocyte and induction of multiple genes into lymphocytes from a recipient for the therapy. We have tried to develop several of these methods and found that a single cell sorting method is so far working for the pairing. Regarding the gene transfer to lymphocytes, a retrovirus vector would be the best. We have succeeded in obtaining more than 50 % of transduction of a single gene. Therefore, more than 10 % of the treated lymphocyte population could express 3 genes altogether. We are now performing experimental immunotherapy for lupus nephritis of NZB/W F1 mice using these established methods.